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Alzheimer's disease: Mechanisms and development of therapeutic strategies
Author(s) -
Tabira Takeshi
Publication year - 2003
Publication title -
geriatrics and gerontology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 57
eISSN - 1447-0594
pISSN - 1444-1586
DOI - 10.1111/j.1444-1586.2003.00082.x
Subject(s) - presenilin , amyloid precursor protein , disease , medicine , apolipoprotein e , senile plaques , alzheimer's disease , amyloid (mycology) , mechanism (biology) , amyloid precursor protein secretase , biochemistry of alzheimer's disease , psen1 , dementia , neuroscience , bioinformatics , biology , pathology , philosophy , epistemology
Senile plaques are the most characteristic change in Alzheimer's disease (AD). In senile plaques, β amyloid is deposited, which is composed of aggregated amyloid β protein (Aβ) derived from amyloid precursor protein (APP). Therefore, it is suggested that there exists a mechanism of increase of Aβ production or a decrease of Aβ degradation and/or clearance of β amyloid in AD. Mutations in familial Alzheimer's disease (FAD) genes such as APP , presenilin 1 ( PS1 ) and presenilin 2 ( PS2 ) result in an increase of Aβ production. Apolipoprotein E (ApoE), a genetic risk factor for AD, is involved in Aβ production and/or its clearance. Thus, it is suggested that an inhibition of Aβ production and a facilitation of β amyloid degradation and clearance delay the clinical onset and progression of AD, and it is possible to cure AD even after an onset of the disease, if it is still at an early phase. Researchers studied the fine mechanisms of Aβ production and identified enzymes that cleave‐out Aβ from APP. Inhibitors of the cleaving enzymes are proven to be effective in ameliorating AD‐like conditions in its animal models and are now being applied to humans. Researchers also found an efficient way of clearing β amyloid deposits using the immune system, which was effective in animal models. When it was applied to humans, some patients developed meningoencephalitis as a side‐effect. Therefore, safer vaccines are now being developed. It did not require 20 years for researchers to develop therapeutic strategies since the discovery of Aβ in 1984. Now that AD is becoming a treatable disease, early diagnosis and early treatment will soon become the rule. Notably, AD may not be a psychiatric disorder any more, and mainly neurologists and geriatricians will see patients. Thus, neurogeriatrics will become more and more important.